title: Masters, marionettes and modulators: intersection of pathogen virulence factors and mammalian death receptor signaling.
abstract: TNF and its receptor, TNFR1, are members of the TNF superfamily and play important roles during infection by orchestrating an inflammatory response. The key role that TNFR1 signaling plays in host defense singles it out as a frequent target of pathogen manipulation. This review describes how the TNFR1 signaling pathway is attacked by pathogen virulence factors and how the different TNFR1 signaling pathways, in particular the death signaling response, have evolved to counteract these pathogen manipulations. We examine recent data showing that other 'Death Receptors' in the TNF superfamily, namely TRAIL-R and Fas, also participate in the immune response to pathogens. Finally we explore how knowledge of the inhibition of these pathways is being translated for clinical applications.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia. Electronic address: j.silke@latrobe.edu.au.
authors.forename: John
authors.initials: J
authors.lastname: Silke
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hartland
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology; D006801:Humans; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology*
chemical_list: D053222:Fas Ligand Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; D053221:TNF-Related Apoptosis-Inducing Ligand; D037521:Virulence Factors